Various errors can occur in the endocannabinoid system, each causing a unique set of symptoms. Proof for any endocannabinoid deficiency is often lacking, but poor ECS function causes particular conditions according to good science. And the deficit is based on causation and not simply correlation.
Raphael Mechoulam discovered anandamide in 1992 and 2-AG a few years afterwards. (1, 2) Following the discovery of endocannabinoids, scientists began studying their role in health and disease. Conclusively, endocannabinoids are critical in almost all human illnesses. (3) In 2001, proof of an ECS deficiency was vague and primarily based on correlation. (4) Skipping ahead twenty years and quantifiable results in peer-reviewed journals now provide good evidence of Clinical Endocannabinoid Deficiency.
Finding proof of an endocannabinoid deficiency
2001 — Ethan Russo, M.D. first hypothesizes the role of Clinical Endocannabinoid deficiency (cECD) in headaches. (4)
2003 — An Italian study analyzed endocannabinoid levels in blood samples of women with migraine. (5)
2004 and 2008 — Russo flushes out his theory on endocannabinoid deficiency. (6)
2007-2008 — Further Italian studies documented endocannabinoid levels in migraine patients. (7, 8) One study collected cerebrospinal fluid from the spines of three dozen participants, including the twenty control subjects. (9)
2009 — Daniele Piomelli led a study on endocannabinoid levels in the spinal fluid of psychosis patients. The team discovered an inverse correlation between anandamide and psychosis. (10)
2009 — Researchers from Manchester University elucidated genetic deficiencies in CB1 receptors that can cause migraine. (11)
2012 — Chronic consumption of pain medication caused deficiencies in the endocannabidiome detected in blood (platelet) samples. (8, 12)
2013 — Researchers discovered a gene responsible for CB1 expression in Irritable Bowel Syndrome, providing some proof of an endocannabinoid deficiency in the condition. (13)
The old theory reconsidered
2016 — Russo revisits his hypothesis on cECD. (14)
2019 — Endocannabinoid levels, analyzed by blood (serum) samples, were deficient in children with Autism Spectrum Disorder. (15)
2020-2022 — Several studies note a deficient endocannabidiome following Covid-19 infection.
2022 — Max Plank Institute teamed up with Harvard Medical School and discovered one more root cause of poor 2-AG function. (16)
2022 — Endocannabinoid levels were not disrupted in resting veterans with PTSD, remembering that endocannabinoids often function on-demand during stress. (17)
Testing endocannabinoids in human tissue
Blood samples (platelets, plasma, or serum) — mildly invasive for patients and a fast collection method, but not a long-term storage site for endocannabinoids. Good for testing on-demand functions.
Cerebrospinal fluid — strong results for researchers and a long-term storage site for endocannabinoids, but the collection is highly invasive for patients.
PET (Positron Emission Tomograph)image test — Boston Children’s Hospital developed an imaging test for the detection of MAG-l, which chews up 2-AG, in brown tissue. The image test requires a radioactive ligand and has only been tested for MAG-l in mice. But the study provides early proof that an endocannabinoid deficiency plays a role in mammalian metabolic disorders. (18)
Diet and routine before supplementation
Is cannabis genuinely essential? Perhaps phytocannabinoids are required for adequate health. But an endocannabinoid system can properly function without cannabis. Fats are crucial in our diet, though. And endocannabinoids are produced from phospholipids or dietary omega-3 fat.
Genetic predispositions or inflammation after a physical injury can rapidly degrade the endocannabinoid system. In these circumstances, supplementing the ECS with specific varieties of cannabis can provide benefits. Keep in mind that THC is not always the answer. In any case, proper diet and routine help to avoid endocannabinoid deficiencies caused by poor life choices.
Let us know your thoughts on the possibility of ECS deficiencies. Do you think there is enough proof to diagnose patients with cECD?
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